|Publication number||US4832851 A|
|Application number||US 07/009,990|
|Publication date||May 23, 1989|
|Filing date||Feb 2, 1987|
|Priority date||Feb 2, 1987|
|Also published as||DE3803067A1, DE3803067C2|
|Publication number||009990, 07009990, US 4832851 A, US 4832851A, US-A-4832851, US4832851 A, US4832851A|
|Inventors||William F. Bowers, Douglas B. Tiffany|
|Original Assignee||W. R. Grace & Co.|
|Export Citation||BiBTeX, EndNote, RefMan|
|Patent Citations (19), Referenced by (105), Classifications (31), Legal Events (7)|
|External Links: USPTO, USPTO Assignment, Espacenet|
The present invention relates to methods and apparatus for filtering a fluid, and more particularly relates to the use of centrifugal force to aid such filtration.
It is well known that the filtration of fluids by microporous and ultraporous filters may be carried out under the influence of centrifugal force. For example, it is often desired to isolate proteins from liquid samples of bodily fluids or biological growth media in order either to concentrate the proteins or to produce a protein-free filtrate. U.S. Pat. No. 3,488,768 (P.N. Rigopulos, 1970) discloses several apparatus and methods for performing such filtration. Rigopulos also teaches that in addition to providing the trans-membrane force necessary to move the liquid through the filter, centrifugal force can be used to maintain the working surface of the filter free from a clogging build-up of protein or sediment.
U.S. Pat. No. 3,960,727 (Hochstrasser) discloses methods and apparatus for separating blood serum from clotted whole blood, preferably aided by centrifugal force. A sample to be filtered is contained in a first tube and a second tube, including a filter at its lower end, is placed therein. The second tube slowly sinks down into the first tube and through the sample, filtering the sample as it sinks. Sinking is advantageously accelerated by subjecting the assembly to centrifugal force by spinning the assembly in a centrifuge.
We have found that during the filtration of rather dilute solutions, such as dilute solutions of proteins or polypeptides, the "full floating" inner filtration tube design of Hochstrasser does not provide optimal trans-membrane pressure during centrifugation. Other problems occur in other devices during the filtration of highly concentrated solutions or solutions containing a large volume of particulate matter, as the filter may rapidly become clogged by the solute or particles. A need remains for apparatus and methods of performing centrifugal force-enhanced filtration of fluids.
An object of the present invention is to provide filtration methods and apparatus useful for both dilute solutions and particle-laden samples.
Another object of the present invention is to provide such an apparatus which, when placed within a 50 ml centrifuge tube carrier, is capable of filtering a 5 to 15 ml volume of sample.
A further object of this invention is to provide complete containment of biohazardous samples during centrifugal force-enhanced filtration.
The present invention satisfies these needs by providing methods and apparatus for filtering a fluid, including both relatively dilute solutions of e.g. protein(s) or polypeptide(s) and relatively particulate samples such as fermentation broth containing cells or whole blood. The apparatus consists of a container for holding a sample of liquid to be filtered, the container having an open end and a closed end. A filtering vessel is installed within the container and includes a chamber for receiving filtered fluid. The filtering vessel is preferably cylindrical and has an open upper end and an opening at its lower end which is covered by a filter, preferably an ultrafiltration (i.e. pore size of less than about 100 Angstroms) membrane carried by a filter support. High trans-membrane pressure and filtration rates are obtained by forcibly immersing the end of the filtering vessel which carries the filter into the sample to create a pressure head above the filter. By "forcibly immersing" we mean immersing against the natural buoyancy of the filtering vessel. The immersed position of the filtering vessel must be maintained, and this is accomplished in our preferred embodiment by the combination of an annular locking cap and the engagement of a ridge on the filtration vessel with the inner edge of the annular cap. Although the pressure differential created by forcible immersion alone may not be sufficient to accomplish filtration, this pressure differential is greatly increased when, according to the inventive method, the apparatus is subjected to centrifugal force. The centrifugal force greatly amplifies the pressure differential between the inside and outside of the filtration vessel to force the sample liquid through the filter and into the filtration vessel. The centrifugal force simultaneously prevents the working side of the filter from becoming clogged with sediment. Liquid within the filtration vessel is known as "filtrate" while that portion of the sample remaining outside the filtration vessel is known as "retentate".
FIG. 1 is an exploded view of the present invention.
FIG. 2 is a view of the present invention prior to centrifugation;
FIG. 3A is a view of the present invention following centrifugation and filtration of a highly concentrated or particle-laden sample;
FIG. 3B is a view of the present invention following centrifugation and filtration of a dilute sample;
FIG. 4 is a plot of retentate volume vs. centrifugation time;
FIG. 5 is a plot of ultrafiltrate volume vs. centrifugation time; and
FIG. 6 is a plot of ultrafiltrate volume vs. centrifugation time.
A preferred embodiment of the present filtration apparatus i illustrated in FIG. 1. The apparatus consists of a container 10 for holding a sample of fluid to be filtered, and in this preferred embodiment container 10 is an elongate tube having a sealed lower end 20 and an open upper end 30. A filtering vessel 40, which in this preferred embodiment also is an elongate tube, is adapted to fit inside of container 10. container 10 and filtering vessel 40 preferably are constructed of a synthetic plastic material which is inert to the fluids likely to be filtered in this apparatus, including bodily fluids and organic solvents. The apparatus preferably is dimensioned to fit within centrifuge rotors designed to accept standard 50 ml centrifuge tubes.
As seen in FIG. 1, the preferred filtering vessel 40 consists of a chamber portion 60 which had a diameter only slightly less than the diameter of the container 10. Chamber portion 60 is connected via a shoulder portion 65 to intermediate diameter to an elongate, narrow neck portion 50. The open lower end 62 of the filtering vessel 40 carries a filter which preferably includes a porous filter support 70 and a filter element 80. Filter element 80 may be of any desired pore size and is chosen with the size of the solute or particle to be filtered in mind. In the figures, filter element 80 is represented as a membrane filter in which case filter support 70 preferably consists of a molded plastic grid having channels and one or more ducts to pass permeate. Support 70 and filter 80 are secured to filtering vessel 40 by crimping lip 63 at the base of vessel 40 and bending the lip over the edge of the filter element and support. In the alternative, support 70 and filter 80 may be cemented to the base of vessel 40. Filter support 70 and filter element 80 may be replaced by other filtering materials, such as open cell foams, a wide variety of which are well known.
As seen in the Figures, this preferred embodiment of the present apparatus includes a first cap 80 which is adapted to maintain the filtering vessel 40 forcibly immersed within the sample in container 10 throughout the filtering process. First cap 80 has a base portion 85 which is adapted to engage the upper portion 30 of container 10, this engagement creating an airtight seal between first cap 80 and container 10. The base portion 85 carries a plurality of teeth 87 which engage corresponding teeth 37 on container 10 to provide a "bayonet"- type lock therebetween. A neck portion 89 of first cap 80 engages filtering vessel 40 via a friction fit between itself and the upper reduced-diameter portion of neck 50 of the filtering vessel, allowing filtrate to be decanted without leakage of retentate. The inner corner 84 of first cap 80 is of smaller diameter than filtering vessel 40 at ridge 41 to provide forcible immersion of the filtering vessel.
A second cap, designated by reference numeral 90, is responsible for sealing the contents of the filtering vessel 40 within the apparatus. As seen in the Figures, second cap 90 is adapted to fit tightly over the neck portion 81 of first cap 80 so that a friction fit is formed therebetween.
During filtration of the fluid sample, the sample passes from container 10, through filter 80 and filter support 70, and into the chamber portion 60 of filtering vessel 40. The air occupying the filtering vessel is displaced by the rising volume of filtrate and passes to chamber 10 via a thin capillary channel 100 formed in the outer surface of neck 50. Channel 100 is dimensioned to that the retentate will not pass therethrough during decantation.
FIG. 2 illustrates an assembled filtration apparatus which has been filled with about 15 ml of a fluid to be filtered. As seen, the shoulder and neck portions of filtering vessel 40 provide a reservoir for the fluid within the upper portion of container 10, although some of the sample occupies the space beneath filter 80 in a reservoir portion now present beneath the filtering vessel. Filtering vessel 40 has been forcibly immersed within into container 10 to create a pressure head (h) above filter 80. The device is now ready to be seated in a centrifuge rotor for centrifugation at a speed and g-force appropriate for the particular sample being filtered.
When centrifugation commences filtration vessel 40, under greatly increased buoyant fluid force from the sample, tries to rise within the container. Vessel 40 is maintained forcibly immersed, as ridge 41 on the neck of vessel 40 contacts the inner edge 84 of the cap 80 as seen FIG. 2. The filtration of particle-laden samples, such as fermentation broth, is facilitated as a reservoir 110 for particles is created below the filtration membrane. The membrane would rapidly become clogged by the large volume of filtered particles if the reservoir were not formed.
FIG. 3A illustrates the present device following filtration of a particle-laden sample. Filtration vessel 40 containing the filtered liquid (filtrate) is resting on a bed of filtered particles contained within the reservoir 110 below the filter. The filtrate is easily decanted by removing second cap 90 and pouring out the liquid. The tight fit between first cap 80, the container 10 and filtering vessel 40 prevents the retentate from leaking during the quick decanting step. The combination of container 10 and first and second caps 80, 90 form an airtight barrier and thus none of the sample escapes as an aerosol.
FIG. 3b illustrates the present device following filtration of a much more dilute sample. Without a bed of particles to rest on, the filtration vessel 40 has sunk to the bottom of container 10 as the vessel has filled with filtrate. Approximately 3 to 3.5 of the original 15 ml of sample remains as retentate, thus providing about a five-fold concentration in the first spin. The filtrate may be decanted and the device reassembled for further centrifugation and filtration. A second filtration provides up to a 15 to 20-fold overall final concentration level.
The following examples illustrate the speedy and efficient filtration/concentration obtainable with the present invention when filtering a variety of samples:
A Dilute Protein Solution
Four devices according to the present invention ("Centriprep™ 10", "10" signifying the 10,000 MW cut-off of the device's filtration membrane) were loaded with 5, 10 or 15 ml of a 1 mg/ml solution of bovine serum albumin and spun in a horizontal or fixed angle (45°) rotor for various lengths of time at 3000×g. After each spin the retentate volumes were determined by direct weight. Each data point up to the first equilibrium (FIG. 4, first spin) was generated with fresh devices. When the first equilibrium was reached, the filtrate was decanted, and the units were reassembled and respun for varying lengths of time. Since the curves for both rotors were very similar, the values for each point were averaged and plotted as one curve per starting volume (FIG. 4).
The data show that a dilute protein solution may be concentrated 20 fold in 55 to 75 minutes depending on the starting volume. During the first spin, approximately a five fold concentration can be achieved before the fluid levels inside and outside the filtering vessel come to equilibrium and filtration stops. After decanting filtrate, the device is spun again until the inner and outer fluid levels reach equilibrium, and a final 20 fold concentration factor is achieved. The final volume of the retentate is 0.5 to 0.7 ml.
The data below show the centrifugation times at 3000×g needed to achieve a certain concentration factor for both Centriprep and Amicon's other centrifugal concentrator, Centricon®. Centricon® is described in U.S. Pat. No. 4,632,761 which is incorporated by reference herein.
______________________________________ Initial Concen- Unit Flux Vol- tration Time Flux (ml/min/Device ume Factor (min) (ml/min) cm2)______________________________________Centriprep 10 15 5 45 .273 .096Centricon 10 2 5 45 .036 .039Centriprep 10 15 10 54 .233 .082Centricon 10 2 10 93 .019 .021Centriprep 10 15 20 63 .222 .078Centricon 10 2 20 107 .017 .019______________________________________ Centriprep 10 provides a twenty fold concentration starting with 15 ml, in less than seventy-five minutes. The overall flux was 0.222 ml/min, with a unit flux of 0.078 ml/min/cm2 for this 2.84 cm2 membrane area device. In the conventional Centricon, a twenty fold concentration beginning with 2 ml tool 110 minutes. Here, the overall flux was 0.017 ml/min, and the unit flux was 0.019 ml/min/cm2. Centriprep 10, with three times the membrane surface area of Centricon provides thirteen times the absolute flux and four times the normalized flux during a twenty fold concentration of dilute protein.
A Concentrated Protein Solution
Four Centriprep 30 devices (i.e., devices according to the present invention having a 30,000 MW cut-off membrane filter) were loaded with 15 ml of whole bovine serum and centrifuged for various lengths of time in a horizontal or fixed angle rotor at 3000×g. After each spin the ultrafiltrate was decanted and weighed. The data for both rotors were again averaged because of the good agreement, and plotted as one curve (FIG. 5).
The data demonstrate that even with concentrated, viscous protein solutions (approximately 80 mg/ml) several ml of protein free filtrate can be produced in a single 20 to 30 minute spin. Filtration rates are high becuase the filtrate vessel is allowed to float above the dense polarizing layer of protein in the bottom of the container tube.
When compared with Centrifree™ (Amicon's centrifugal device designed to produce protein free filtrate from serum), Centriprep had over twice the unit flux (ml/min/cm2) at any given concentration factor.
A Particulate-Containing Solution
Four Centriprep 10 devices were spun with 5, 10 and 15 ml of lysed yeast (15% wt/vol) for different lengths of time at 3000×g in a horizontal rotor. Cell free filtrates were weighed after each spin and the data plotted in FIG. 6.
By limiting the starting volume to 5 ml, and thereby minimizing the volume of particulates that can pack around and blind the membrane, the filtration rate can be sustained to yield a cell free filtrate volume of greater than 1.0 ml in a single 20 minute spin. Once again the filtration rate is optimized because the filtrate vessel is allowed to float above the packed layer of cells at the bottom of the container tube.
By contrast, with Centricon 10, only 0.12 ml of filtrate can be obtained from 2 ml of 15% yeast in 20 minutes. Increasing the spin time does not significantly increase the filtrate volume (0.185 ml after 60 minutes) because the Centricon, flow is greatly reduced due to the layer of cells packed directly on the membrane surface.
Protein Recovery After Sample Concentration In Centriprep
Centriprep 30 and Centriprep 10 were loaded with 15 ml of 1 mg/ml bovine serum albumin and 15 ml of 0.25 mg/ml cytochrome C respectively. All devices were spun to their first equilibrium point and the filtrate was decanted. Devices were then spun to their second equilibrium point and the final filtrate was decanted and combined with the first. Filtrates, concentrates and starting material were weighed and assayed for protein, and percent recoveries were calculated. The following data demonstrate the excellent yield of samples concentrated in Centriprep.
______________________________________ Recovery from Recovery fromDevice Filtrate Retentate n______________________________________Centriprep 30 2.9 ± 2.1 93.6 ± 2.8 20Centriprep 10 2.3 ± 2.8 95.8 ± 3.7 40______________________________________
|Cited Patent||Filing date||Publication date||Applicant||Title|
|US1386340 *||Aug 2, 1920||Aug 2, 1921||Wuster Robert||Filtering apparatus|
|US3481477 *||Mar 2, 1965||Dec 2, 1969||Andrew F Farr||Apparatus for filtering out clear liquid from suspended solids|
|US3488768 *||Feb 8, 1968||Jan 6, 1970||Amicon Corp||Self-cleaning ultrafilter|
|US3508653 *||Nov 17, 1967||Apr 28, 1970||Charles M Coleman||Method and apparatus for fluid handling and separation|
|US3512940 *||Dec 30, 1968||May 19, 1970||Lab Ind||Test tube filter device|
|US3661265 *||Jul 27, 1970||May 9, 1972||Contemporary Research And Dev||Serum separator type container|
|US3693804 *||Apr 29, 1971||Sep 26, 1972||Douglas U Grover||Pressure differential filtering apparatus and method|
|US3761408 *||May 8, 1972||Sep 25, 1973||Jae Yoon Lee||Method and apparatus for separating blood constituent components|
|US3782548 *||Dec 7, 1972||Jan 1, 1974||J Bowen||Serum skimmer|
|US3799342 *||Jun 23, 1972||Mar 26, 1974||Medical Res & Dev Inc||Method of using a serum separator|
|US3814248 *||Feb 23, 1972||Jun 4, 1974||Corning Glass Works||Method and apparatus for fluid collection and/or partitioning|
|US3814258 *||Mar 15, 1973||Jun 4, 1974||Dickinson And Co||Blood plasma separator with filter|
|US3832141 *||Jan 3, 1973||Aug 27, 1974||Glasrock Products||Pressure differential filtering apparatus|
|US3960727 *||Aug 9, 1974||Jun 1, 1976||Hochstrasser Harry T||Apparatus and method for isolating soluble blood components|
|US4035150 *||Jul 7, 1976||Jul 12, 1977||The United States Of America As Represented By The Secretary Of The Department Of Health, Education And Welfare||Test for occult blood in an emulsified aqueous/organic system|
|US4483825 *||Jul 9, 1982||Nov 20, 1984||Fatches Keith R||Pipette and filter combination|
|US4522713 *||Nov 25, 1983||Jun 11, 1985||Sartorius Gmbh||Apparatus for static membrane filtration|
|US4632761 *||Aug 15, 1983||Dec 30, 1986||W. R. Grace & Co.||Centrifugal microconcentrator and methods for its use|
|GB2133306A *||Title not available|
|Citing Patent||Filing date||Publication date||Applicant||Title|
|US5112484 *||Oct 11, 1990||May 12, 1992||Zuk, Inc.||Filtration apparatus|
|US5124041 *||May 1, 1991||Jun 23, 1992||Applied Biosystems, Inc.||Biomolecule sample immobilization|
|US5508196 *||May 7, 1993||Apr 16, 1996||Westfalia Separator Ag||Method of continuously preparing a sterile culture medium|
|US5552325 *||Jul 17, 1992||Sep 3, 1996||Fmc Corporation||Method for separation and recovery of biological materials|
|US5556544 *||Sep 8, 1995||Sep 17, 1996||Didier; Emmanuel R.||Concentrator & filter|
|US5585007 *||Dec 7, 1994||Dec 17, 1996||Plasmaseal Corporation||Plasma concentrate and tissue sealant methods and apparatuses for making concentrated plasma and/or tissue sealant|
|US5610074 *||Feb 24, 1993||Mar 11, 1997||Beritashvili; David R.||Centrifugal method and apparatus for isolating a substance from a mixture of substances in a sample liquid|
|US5658463 *||Jun 7, 1995||Aug 19, 1997||Strategic Diagnostics, Inc.||Process for extraction of analytes from solid and materials and filtration|
|US5728267 *||Nov 15, 1994||Mar 17, 1998||Flaherty; James E.||Concentrator for separating small samples in a centrifuge|
|US5733449 *||Dec 8, 1995||Mar 31, 1998||Orbital Biosciences, Llc||Microconcentrator device|
|US5741423 *||Aug 23, 1995||Apr 21, 1998||Bates; John||Liquid-liquid extraction|
|US5783087 *||Aug 29, 1997||Jul 21, 1998||Millipore Investment Holdings Limited||Method and apparatus for isolation and purification of immune complexes|
|US5788662 *||Oct 22, 1996||Aug 4, 1998||Plasmaseal Llc||Methods for making concentrated plasma and/or tissue sealant|
|US5855848 *||Mar 3, 1995||Jan 5, 1999||Sanitaria Scaligera S.P.A.||Centrifuge apparatus for carrying out immunohaemtological analysis of blood and other biological liquids|
|US6017698 *||Apr 1, 1996||Jan 25, 2000||Roche Diagnostics Gmbh||Method of binding a biological material|
|US6063297 *||Aug 3, 1998||May 16, 2000||Plasmaseal Llc||Method and apparatus for making concentrated plasma and/or tissue sealant|
|US6214338 *||Apr 25, 2000||Apr 10, 2001||Plasmaseal Llc||Plasma concentrate and method of processing blood for same|
|US6302919||Jul 20, 1999||Oct 16, 2001||Brian Chambers||Reverse-flow centrifugal filtration method|
|US6355174||Sep 21, 2000||Mar 12, 2002||Phoenix Medical Limited||Method of separating foetal trophoblasts from maternal blood|
|US7074333||Jan 19, 2001||Jul 11, 2006||Millipore Corporation||Recovery of linear nucleic acids by salt dilution and/or reduced pressure prior to continuous pressure differential ultrafiltration|
|US7374678||Sep 2, 2004||May 20, 2008||Biomet Biologics, Inc.||Apparatus and method for separating and concentrating fluids containing multiple components|
|US7470371||Oct 19, 2006||Dec 30, 2008||Hanuman Llc||Methods and apparatus for isolating platelets from blood|
|US7686965||May 31, 2007||Mar 30, 2010||Cook Melvin W||Centrifugal fluid filtration devices, systems and methods|
|US7708152||Jan 30, 2006||May 4, 2010||Hanuman Llc||Method and apparatus for preparing platelet rich plasma and concentrates thereof|
|US7780860||May 19, 2008||Aug 24, 2010||Biomet Biologics, Llc||Apparatus and method for separating and concentrating fluids containing multiple components|
|US7806276||Apr 11, 2008||Oct 5, 2010||Hanuman, Llc||Buoy suspension fractionation system|
|US7824559||Jan 30, 2006||Nov 2, 2010||Hanumann, LLC||Apparatus and method for preparing platelet rich plasma and concentrates thereof|
|US7832566||May 25, 2006||Nov 16, 2010||Biomet Biologics, Llc||Method and apparatus for separating and concentrating a component from a multi-component material including macroparticles|
|US7837884||Dec 29, 2008||Nov 23, 2010||Hanuman, Llc||Methods and apparatus for isolating platelets from blood|
|US7845499||May 25, 2006||Dec 7, 2010||Biomet Biologics, Llc||Apparatus and method for separating and concentrating fluids containing multiple components|
|US7866485||Jul 31, 2007||Jan 11, 2011||Hanuman, Llc||Apparatus and method for preparing platelet rich plasma and concentrates thereof|
|US7914689||May 19, 2008||Mar 29, 2011||Biomet Biologics, Llc||Apparatus and method for separating and concentrating fluids containing multiple components|
|US7987995||May 3, 2010||Aug 2, 2011||Hanuman, Llc||Method and apparatus for preparing platelet rich plasma and concentrates thereof|
|US7992725||Apr 11, 2008||Aug 9, 2011||Biomet Biologics, Llc||Buoy suspension fractionation system|
|US8012077||May 23, 2008||Sep 6, 2011||Biomet Biologics, Llc||Blood separating device|
|US8048321||Aug 11, 2010||Nov 1, 2011||Biomet Biologics, Llc||Apparatus and method for separating and concentrating fluids containing multiple components|
|US8062534||Dec 6, 2010||Nov 22, 2011||Biomet Biologics, Llc||Apparatus and method for separating and concentrating fluids containing multiple components|
|US8096422||Nov 1, 2010||Jan 17, 2012||Hanuman Llc||Apparatus and method for preparing platelet rich plasma and concentrates thereof|
|US8105495||Jan 10, 2011||Jan 31, 2012||Hanuman, Llc||Method for preparing platelet rich plasma and concentrates thereof|
|US8119013||Oct 4, 2010||Feb 21, 2012||Hanuman, Llc||Method of separating a selected component from a multiple component material|
|US8133389||Jul 29, 2011||Mar 13, 2012||Hanuman, Llc||Method and apparatus for preparing platelet rich plasma and concentrates thereof|
|US8163184||Mar 25, 2011||Apr 24, 2012||Biomet Biologics, Llc||Apparatus and method for separating and concentrating fluids containing multiple components|
|US8187475||Mar 6, 2009||May 29, 2012||Biomet Biologics, Llc||Method and apparatus for producing autologous thrombin|
|US8187477||Nov 22, 2010||May 29, 2012||Hanuman, Llc||Methods and apparatus for isolating platelets from blood|
|US8216462||Aug 8, 2008||Jul 10, 2012||O'brien Paul W||Portable drinking water purification device|
|US8313954||Apr 3, 2009||Nov 20, 2012||Biomet Biologics, Llc||All-in-one means of separating blood components|
|US8318011||Oct 15, 2009||Nov 27, 2012||Miracle Straw Corporation, Inc.||Portable drinking water purification device|
|US8328024||Aug 4, 2011||Dec 11, 2012||Hanuman, Llc||Buoy suspension fractionation system|
|US8337711||Feb 27, 2009||Dec 25, 2012||Biomet Biologics, Llc||System and process for separating a material|
|US8394268||Jul 24, 2009||Mar 12, 2013||Miracle Straw Corporation, Inc.||Double chamber water purification device|
|US8394342||Jul 21, 2009||Mar 12, 2013||Becton, Dickinson And Company||Density phase separation device|
|US8425771||Jan 24, 2011||Apr 23, 2013||Miracle Straw Corporation, Inc.||Double chamber water purification device|
|US8567609||Apr 19, 2011||Oct 29, 2013||Biomet Biologics, Llc||Apparatus and method for separating and concentrating fluids containing multiple components|
|US8591391||Apr 12, 2010||Nov 26, 2013||Biomet Biologics, Llc||Method and apparatus for separating a material|
|US8596470||Feb 20, 2012||Dec 3, 2013||Hanuman, Llc||Buoy fractionation system|
|US8603346||Sep 22, 2011||Dec 10, 2013||Biomet Biologics, Llc||Apparatus and method for separating and concentrating fluids containing multiple components|
|US8747781||Jul 21, 2009||Jun 10, 2014||Becton, Dickinson And Company||Density phase separation device|
|US8783470||May 25, 2012||Jul 22, 2014||Biomet Biologics, Llc||Method and apparatus for producing autologous thrombin|
|US8794452||Aug 1, 2013||Aug 5, 2014||Becton, Dickinson And Company||Density phase separation device|
|US8801586 *||Dec 20, 2012||Aug 12, 2014||Biomet Biologics, Llc||System and process for separating a material|
|US8808551||Nov 15, 2010||Aug 19, 2014||Biomet Biologics, Llc||Apparatus and method for separating and concentrating fluids containing multiple components|
|US8950586||Jul 1, 2013||Feb 10, 2015||Hanuman Llc||Methods and apparatus for isolating platelets from blood|
|US8992862||Nov 15, 2012||Mar 31, 2015||Biomet Biologics, Llc||All-in-one means of separating blood components|
|US8998000||May 14, 2010||Apr 7, 2015||Becton, Dickinson And Company||Density phase separation device|
|US9011800||Jul 16, 2009||Apr 21, 2015||Biomet Biologics, Llc||Method and apparatus for separating biological materials|
|US9079123||Aug 6, 2013||Jul 14, 2015||Becton, Dickinson And Company||Density phase separation device|
|US9114334||Dec 9, 2013||Aug 25, 2015||Biomet Biologics, Llc||Apparatus and method for separating and concentrating fluids containing multiple components|
|US9138664||Dec 2, 2013||Sep 22, 2015||Biomet Biologics, Llc||Buoy fractionation system|
|US9144773 *||Aug 9, 2012||Sep 29, 2015||Mekorot Water Company, Ltd||Method for manipulating a membrane element within a pressure vessel|
|US9239276||Oct 28, 2013||Jan 19, 2016||Biomet Biologics, Llc||Apparatus and method for separating and concentrating fluids containing multiple components|
|US9333445||Jul 21, 2009||May 10, 2016||Becton, Dickinson And Company||Density phase separation device|
|US9339741||May 2, 2014||May 17, 2016||Becton, Dickinson And Company||Density phase separation device|
|US9364828||Aug 1, 2013||Jun 14, 2016||Becton, Dickinson And Company||Density phase separation device|
|US9452427||Nov 28, 2012||Sep 27, 2016||Becton, Dickinson And Company||Density phase separation device|
|US9533090||Nov 21, 2013||Jan 3, 2017||Biomet Biologics, Llc||Method and apparatus for separating a material|
|US9556243||Oct 10, 2013||Jan 31, 2017||Biomet Biologies, LLC||Methods for making cytokine compositions from tissues using non-centrifugal methods|
|US9642956||Aug 27, 2012||May 9, 2017||Biomet Biologics, Llc||Apparatus and method for separating and concentrating fluids containing multiple components|
|US9649579||Dec 10, 2012||May 16, 2017||Hanuman Llc||Buoy suspension fractionation system|
|US9682373||Apr 15, 2013||Jun 20, 2017||Becton, Dickinson And Company||Device for separating components of a fluid sample|
|US9694359||Feb 24, 2015||Jul 4, 2017||Becton, Dickinson And Company||Mechanical separator for a biological fluid|
|US9700886||Aug 30, 2016||Jul 11, 2017||Becton, Dickinson And Company||Density phase separation device|
|US9701728||Jul 24, 2015||Jul 11, 2017||Biomet Biologics, Llc||Methods and compositions for delivering interleukin-1 receptor antagonist|
|US20050026175 *||Mar 19, 2004||Feb 3, 2005||John Link||Devices and methods for isolating RNA|
|US20050042660 *||Aug 10, 2004||Feb 24, 2005||Hall Gerald Edward||Devices and methods for isolating RNA|
|US20060099605 *||Nov 11, 2004||May 11, 2006||Hall Gerald E Jr||Devices and methods for isolating RNA|
|US20060175242 *||Jan 30, 2006||Aug 10, 2006||Hanuman Llc||Method and apparatus for preparing platelet rich plasma and concentrates thereof|
|US20060175244 *||Jan 30, 2006||Aug 10, 2006||Hanuman Llc||Apparatus and method for preparing platelet rich plasma and concentrates thereof|
|US20060223072 *||Mar 31, 2005||Oct 5, 2006||Boyes Barry E||Methods of using a DNase I-like enzyme|
|US20060223073 *||Mar 31, 2005||Oct 5, 2006||Boyes Barry E||Methods of using a DNase I-like enzyme|
|US20060270843 *||May 26, 2005||Nov 30, 2006||Hall Gerald E Jr||Methods for isolation of nucleic acids|
|US20070034579 *||Oct 19, 2006||Feb 15, 2007||Randel Dorian||Methods and apparatus for isolating platelets from blood|
|US20070276191 *||May 26, 2006||Nov 29, 2007||Sean Selover||Illuminated surgical access system including a surgical access device and integrated light emitter|
|US20070278146 *||May 31, 2007||Dec 6, 2007||Cook Melvin W||Centrifugal Fluid Filtration Devices, Systems and Methods|
|US20070284319 *||May 31, 2007||Dec 13, 2007||Cook Melvin W||Centrifugal Fluid Filtration Devices, Systems and Methods|
|US20080254058 *||Dec 14, 2005||Oct 16, 2008||Alk-Abello A/S||Pharmaceutical Composition Comprising a Bacterial Cell Displaying a Heterologous Proteinaceous Compound|
|US20100032381 *||Jul 24, 2009||Feb 11, 2010||O'brien Paul W||Double Chamber Water Purification Device|
|US20100155319 *||Jul 21, 2009||Jun 24, 2010||Becton, Dickinson And Company||Density Phase Separation Device|
|US20100155343 *||Jul 21, 2009||Jun 24, 2010||Becton, Dickinson And Company||Density Phase Separation Device|
|US20130140226 *||Sep 20, 2011||Jun 6, 2013||Reapplix Aps||Container for use when producing a multi-layered blood product|
|US20140209538 *||Aug 9, 2012||Jul 31, 2014||Mekorot Water Company, Ltd||Method for manipulating a membrane element within a pressure vessel|
|EP2260943A1||Jun 11, 2009||Dec 15, 2010||Innosieve Diagnostics B.V.||Microfilter centrifuge tube|
|WO1996020776A2 *||Jan 3, 1996||Jul 11, 1996||Pall Corporation||Filtration apparatus|
|WO1996020776A3 *||Jan 3, 1996||Sep 19, 1996||Pall Corp||Filtration apparatus|
|WO2001005507A1 *||Jun 13, 2000||Jan 25, 2001||Biosite Diagnostics, Inc.||Reverse-flow centrifugal filtration method, apparatus and device|
|WO2001005508A1 *||Jul 19, 2000||Jan 25, 2001||Biosite Diagnostics, Inc.||Reverse-flow centrifugal filtration method, apparatus, and device|
|U.S. Classification||210/650, 494/48, 436/178, 210/321.67, 494/16, 210/515, 210/360.1, 210/782, 210/321.84, 210/518, 210/455, 210/380.1, 494/37, 422/534|
|International Classification||B01D65/08, G01N33/49, B01D33/00, B01D63/16, B01D63/08, B01D61/18, B01D61/14, B04B5/02, G01N33/48, B01D61/20|
|Cooperative Classification||B01D33/00, G01N33/491, Y10T436/255, B01D61/18|
|European Classification||B01D33/00, G01N33/49C, B01D61/18|
|Apr 10, 1987||AS||Assignment|
Owner name: W. R. GRACE & CO., 24 CHERRY HILL DRIVE, DANVERS,
Free format text: ASSIGNMENT OF ASSIGNORS INTEREST.;ASSIGNORS:BOWERS, WILLIAM F.;TIFFANY, DOUGLAS B.;REEL/FRAME:004695/0807
Effective date: 19870401
|Aug 24, 1989||AS||Assignment|
Owner name: W. R. GRACE & CO.-CONN., MASSACHUSETTS
Free format text: MERGER;ASSIGNORS:GRACE MERGER CORP. A CT CORP. (MERGED INTO);W. R. GRACE & CO. A CT. CORP.;REEL/FRAME:005206/0001
Effective date: 19880525
|Nov 9, 1992||FPAY||Fee payment|
Year of fee payment: 4
|Jan 8, 1993||AS||Assignment|
Owner name: AMICON, INC., MASSACHUSETTS
Free format text: ASSIGNMENT OF ASSIGNORS INTEREST.;ASSIGNOR:W.R. GRACE & CO. -CONN.;REEL/FRAME:006376/0566
Effective date: 19920629
|Sep 24, 1996||FPAY||Fee payment|
Year of fee payment: 8
|Jun 9, 1997||AS||Assignment|
Owner name: MILLIPORE INVESTMENT HOLDINGS LIMITED, DELAWARE
Free format text: ASSIGNMENT OF ASSIGNORS INTEREST;ASSIGNOR:W.R. GRACE & CO.-CONN. AND AMICON,INC.;REEL/FRAME:008587/0224
Effective date: 19961231
|Sep 28, 2000||FPAY||Fee payment|
Year of fee payment: 12